Insulin resistance and impaired pancreatic β-cell function in adult offspring of women with diabetes in pregnancy

Abstract

Context: Offspring of women with diabetes during pregnancy have an increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown. Objective: We aimed to investigate the effects of intrauterine hyperglycemia on insulin secretion and action in adult offspring of mothers with diabetes. Design, Setting, and Participants: A cohort of 587 Caucasian offspring, without known diabetes, was followed up at the age of 18-27 years. We included 2 groups exposed to maternal diabetes in utero: offspring of women with gestational diabetes mellitus (n = 167) or type 1 diabetes (n =153). Two reference groups were included: offspring of women with risk factors for gestational diabetes mellitus but normoglycemia during pregnancy (n = 139) and offspring from the background population (n = 128). Main Outcome Measures: Indices of insulin sensitivity and insulin release were calculated using insulin and glucose values from a standard oral glucose tolerance test (120 minutes, 75 g glucose). Pancreatic β-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices. Results: Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes had reduced insulin sensitivity compared with offspring from the background population (both P < .005). Conclusion: Reduced insulin sensitivity as well as impaired pancreatic β-cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy. Copyright © 2013 by The Endocrine Society.